Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California.
Department of Psychology, Stanford University, Stanford, California.
JAMA Psychiatry. 2014 Oct;71(10):1148-56. doi: 10.1001/jamapsychiatry.2014.1031.
Bipolar disorder (BD) is highly familial and characterized by deficits in reward processing. It is not known, however, whether these deficits precede illness onset or are a consequence of the disorder.
To determine whether anomalous neural processing of reward characterizes children at familial risk for BD in the absence of a personal history of a psychopathologic disorder.
DESIGN, SETTING, AND PARTICIPANTS: This study compared neural activity and behaviors of children at high and low risk for mania while they anticipate and respond to reward and loss. The study was performed from September 15, 2009, through February 17, 2012, in a university functional magnetic resonance imaging facility and included 8- to 15-year-old children without disorders born to a parent with BD (n = 20 high-risk children) and demographically matched healthy comparison children (n = 25 low-risk children).
Neural activity, as measured with functional magnetic resonance imaging, during anticipation and receipt of reward and loss during a monetary incentive delay task.
While anticipating losses, high-risk children had less activation in the pregenual cingulate than did their low-risk counterparts (t19 = -2.44, P = .02). When receiving rewards, high-risk children had greater activation in the left lateral orbitofrontal cortex than did low-risk children (t43 = -3.04, P = .004). High-risk children also had weaker functional connectivity between the pregenual cingulate and the right ventrolateral prefrontal cortex while anticipating rewards than did low-risk children (t19 = -4.38, P < .001) but had a stronger connectivity between these regions while anticipating losses (t24 = 2.76, P = .01). Finally, in high- but not low-risk children, novelty seeking was associated with increased striatal and amygdalar activation in the anticipation of losses, and impulsivity was associated with increased striatal and insula activation in the receipt of rewards.
Aberrant prefrontal activations and connectivities during reward processing suggest mechanisms that underlie early vulnerabilities for developing dysfunctional regulation of goal pursuit and motivation in children at high risk for mania. Longitudinal studies are needed to examine whether these patterns of neural activation predict the onset of mania and other mood disorders in high-risk children.
双相障碍（BD）具有高度家族性，其特征是奖励处理缺陷。然而，尚不清楚这些缺陷是在疾病发作之前出现的，还是疾病的后果。
确定在没有精神病理障碍个人病史的情况下，BD 的家族高危儿童是否存在异常的奖励神经处理。
设计、环境和参与者：本研究比较了高风险和低风险儿童在预期和应对奖励和损失时的神经活动和行为。该研究于 2009 年 9 月 15 日至 2012 年 2 月 17 日在大学功能磁共振成像设施中进行，包括无障碍的父母一方患有双相障碍（BD）的 8 至 15 岁儿童（n=20 名高风险儿童）和在人口统计学上与之匹配的健康对照儿童（n=25 名低风险儿童）。
使用功能磁共振成像在货币奖励延迟任务期间预测和获得奖励和损失时的神经活动。
在预期损失时，高风险儿童的前扣带回皮质比低风险儿童的激活程度更低（t19=-2.44，P=.02）。当接受奖励时，高风险儿童的左侧外侧眶额皮质的激活程度大于低风险儿童（t43=-3.04，P=.004）。高风险儿童在预测奖励时，前扣带回皮质与右侧腹外侧前额叶皮质之间的功能连接也比低风险儿童弱（t19=-4.38，P<.001），但在预测损失时的连接更强（t24=2.76，P=.01）。最后，在高风险但不在低风险儿童中，对新奇事物的寻求与对损失的预测中纹状体和杏仁核的激活增加有关，冲动与对奖励的接收中纹状体和岛叶的激活增加有关。
奖励处理过程中前额叶的异常激活和连接表明，在易患躁狂的儿童中，存在导致目标追求和动机的功能失调调节的早期脆弱性的机制。需要进行纵向研究，以检查这些神经激活模式是否可以预测高危儿童的躁狂和其他情绪障碍的发作。
